Implanted medical devices such as venous and arterial catheters, neurological prostheses, wound drains, urinary “Foley” catheters, peritoneal catheters, and other lumenal in-dwelling devices, have been useful for treating various medical conditions. However, a drawback to implanted medical devices is the risk of infection while the medical device is inserted in the body, and thereafter. Such risk exists even though the medical devices are sterilized and carefully packaged to guard against introduction of microbes or pathogens during implantation or insertion of the medical device. For example, there is a risk of serious nosocomial infections when using catheters for hemodialysis procedures. In fact, central venous catheters account for most nosocomial catheter-related bloodstream infections.
When catheters and other in-dwelling luminal devices are inserted into body cavities such as the urinary tract, venous or arterial vessels, bacteria or other microbes can be picked up from the skin or the catheter hub, lumen or infusate and transfered onto the insertion site where bacterial or microbial colonization may ensue. Once the microorganisms adhere to the catheter surface, it colonizes the surface. These bacteria enhance their adherence rapidly by producing an extracellular slime that makes up the microbial substance of the biofilm. The biofilm layer made of microbial and host substances acts as a protective barrier.
In the case of urinary and venous catheters, there is a significant threat of microbial growth along the exterior surface or outer wall of the catheter and, especially for catheters used long-term, there is a significant threat of microbial grown along the interior surface or inner wall. This can lead to chronic urinary tract infections (CUTI), or septicemia in the case of venous and arterial catheters, thrombolytic emboli, stenosis, and thrombosis resulting from infections, and other life threatening complications, especially among the elderly and immuno-compromised patients. Thus, there is a need for the development of better methods of preventing and treating infections caused by the insertion of catheters into body cavities.
There have been many attempts to prevent such infections. For example, central venous catheters have been developed with chlorohexidine and silver sulfadiazine coatings (ArrowG+ard) and with a combination of minocycline and rifampin coatings (see, e.g., Cook Spectrum™). However, these antiseptic/antibiotic-impregnated catheters have not been adequate, as they have only been shown to reduce the incidence of catheter related infections in the short term, such as less than 30 days. Thus, there is a need for improved catheters that are effective in reducing infections in the long-term.
Iodine-based interventional devices have also been used to minimize the risk of nosocomial bloodstream infection. In particular, an iodine-based, soft, flexible poly-carbonate fiber in the shape of a rod has been placed inside of in-dwelling catheters, as discussed in WO 00/74743 A1. Generally, these polymeric-matrices are chemically and geometrically configured to enable a controlled-release of monomeric iodine at specific conditions such as temperature, making them extremely useful as anti-infective substrates for the effective management of catheter-based nosocomial blood stream infections. Since the surface of the catheter polymer is semi-permeable, the iodine egresses to the exterior surface of the in-dwelling catheter.
Such iodine-loaded rod is inserted into a catheter by gently sliding the rod into the inlet and outlet ports of a lumen of the catheter while holding the rod between the thumb and index fingers. Due to the flexibility of the rod, resistance may be encountered while gently threading it into the lumen. Inserting this rod into the catheter, without contamination, is an arduous and challenging exercise. Even with the use of gloves, there is a potential for contamination. Thus, it is desirable for the rod to remain sterile and, therefore, out of direct contact with equipment, hands, and any other non-sterile surfaces during insertion of the iodine-based rod into the catheter.
Accordingly, there is a need for a medical device that can prevent or reduce the incidences of infection, such as nosocomial infection, during use of medical devices.
Thus, there is a need for an implanted medical device that can more effectively provide anti-infective activity. In particular, there is a need for a medical device that includes a substrate containing an anti-microbial agent that can be inserted into a medical device with a reduced risk of infection at the site of the implanted medical device. There is also a need for a medical device that can provide long-term anti-microbial or anti-infection activity.
There is a further need for an improved method of making such a medical device having anti-infective activity. There is also a need for a method in which an anti-infective substrate is inserted into a medical device such as a catheter in a manner that maintains the sterility and strength of the substrate during insertion.